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We skip to work: alternative splicing in normal and malignant myelopoiesis

Leukemia volume 32, pages 1081–1093 (2018)Cite this article

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Abstract

Alternative splicing expands the transcriptome thereby promoting protein diversity. It governs critical cellular processes such as differentiation, proliferation and apoptosis in a tissue-specific manner. Aberrant splicing consequent to mutations in splicing factors and disruption of isoform ratios in key regulatory genes provides an important contribution to the pathogenesis of the myelodysplastic syndromes and myeloid leukemia. We review here the central role of alternative splicing in regulating myelopoiesis, and provide clear examples of how global splicing disruption or specific aberrant splicing events might promote leukemogenesis. We discuss the growing number of mechanistic links between epigenetic factors and alternative splicing. Finally, we address the potential utility of alternatively spliced isoforms as biomarkers and the development of novel therapies that modulate alternative splicing in myeloid and other malignancies.

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Acknowledgements

JEJR and JJ-LW received funding from by the National Health and Medical Research Council (Grant #1061906 to JEJR, #1129901, #1080530, #1128175 to JEJR and JJ-LW, and #1126306 to JJ-LW.) JEJR was funded by Cure the Future and an anonymous foundation. JJ-LW is a Cancer Institute of New South Wales Fellow.

Author contributions

ACHW and JJ-LW conceived the ideas and structure of the review. ACHW, JEJR JJ-LW were involved in critical analysis of data, writing and revision. All authors approved the final version of the manuscript.

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Authors and Affiliations

  1. Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney, Camperdown, 2050, Australia

    Alex C. H. Wong, John E. J. Rasko & Justin J.-L. Wong

  2. Gene Regulation in Cancer Laboratory, Centenary Institute, University of Sydney, Camperdown, 2050, Australia

    Alex C. H. Wong & Justin J.-L. Wong

  3. Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia

    Alex C. H. Wong, John E. J. Rasko & Justin J.-L. Wong

  4. Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, 2050, Australia

    John E. J. Rasko

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  1. Alex C. H. Wong
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  2. John E. J. Rasko
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  3. Justin J.-L. Wong
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Correspondence to Justin J.-L. Wong.

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Wong, A.C.H., Rasko, J.E.J. & Wong, J.JL. We skip to work: alternative splicing in normal and malignant myelopoiesis. Leukemia 32, 1081–1093 (2018). https://doi.org/10.1038/s41375-018-0021-4

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  • DOI: https://doi.org/10.1038/s41375-018-0021-4

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